Multiple myeloma represents the second most common hematologic malignancy, with nearly 15,000 new cases each year in the United States (Henrick et al., Curr. Opin. Hematol. 5:254 (1998)). The disease is characterized by the malignant proliferation of plasma cells involving more than 10% of the bone marrow (George and Sadovsky, Am. Fam. Physician 59:1885 (1999)). Multiple myeloma cells produce monoclonal immunoglobulins that may be identified with serum or urine protein electrophoresis. The most common clinical manifestations include bone pain, weakness, and fatigue (Kyle, Pathol. Biol. (Paris) 47:148 (1999)).
The standard chemotherapy for multiple myeloma was introduced more than 30 years ago, and since then, there has been little improvement in the overall survival rate (San Miguel et al., Haematologica 84:36 (1999)). Despite a wide variety of chemotherapeutic and supportive treatment options, multiple myeloma is almost invariably fatal (Anderson et al., Semin. Hematol. 36 (Suppl. 3):3 (1999)). While high-dose chemotherapy followed by stem cell transplantation produces higher remission rates, patients are rarely, if ever, cured by a single regimen (Anderson et al., Semin. Hematol. 36 (Suppl. 3):3 (1999)). Relapse is inevitable in all but a small number of cases, and for the majority of cases, treatment only produces, at best, periods of remission with minimal treatment-related morbidity and mortality (Smith and Newland, QJM 92:11 (1999)). The aggregate median survival for all stages of multiple myeloma is about three years (Henrick et al., Curr. Opin. Hematol. 5:254 (1998); George and Sadovsky, Am. Fam. Physician 59:1885 (1999)).
Accordingly, a need still exists for improved methods of treating multiple myeloma.